It remains unclear whether white matter (WM) changes found in post-traumatic stress disorder (PTSD) patients are stress-induced or precursors for vulnerability. The current study aimed to identify susceptibility factors relating to the development of PTSD and to examine the ability of these factors to predict the course of longitudinal PTSD. Sixty two victims who had experienced traffic accidents underwent diffusion tensor imaging using a 3.0T MRI system within 2 days after their accidents. Of these, 21 were diagnosed with PTSD at 1 or 6 months using the Clinician-Administered Ptsd Scale (CAPS). Then, 11 trauma-exposed victims with PTSD underwent the second MRI scan. Compared with the victims without PTSD, the victims with PTSD showed decreased fractional anisotropy (FA) in WM of the anterior cingulate cortex, ventromedial prefrontal cortex (vmPFC), temporal lobes and midbrain, and increased mean diffusivity (MD) in the vmPFC within 2 days after the traumatic event. Importantly, decreased FA of the vmPFC in the acute phase predicted greater future CAPS scores. In addition, we found decreased FA in the insula in the follow-up scan in the victims with PTSD, which correlated with the decreased FA of the vmPFC in their baseline scan. These results suggested that the WM might have changed within 2 days after the traumatic event in the individuals who would later develop PTSD. Furthermore, decreased FA of the vmPFC could be a possible vulnerability marker predicting future development of PTSD and may provide an outcome prediction of the acquired signs.
Arl1 is a member of Arf family small GTPases that is essential for the organization and function of Golgi complex. Mon2/Ysl2, which shares significant homology with Sec7 family Arf guanine nucleotide exchange factors, was poorly characterized in mammalian cells. Here, we report the first in depth characterization of mammalian Mon2. We found that Mon2 localized to trans-Golgi network which was dependent on both its N and C termini. The depletion of Mon2 did not affect the Golgi localized or cellular active form of Arl1. Furthermore, our in vitro assay demonstrated that recombinant Mon2 did not promote guanine nucleotide exchange of Arl1. Therefore, our results suggest that Mon2 could be neither necessary nor sufficient for the guanine nucleotide exchange of Arl1. We demonstrated that Mon2 was involved in endosome-to-Golgi trafficking as its depletion accelerated the delivery of furin and CI-M6PR to Golgi after endocytosis.
There is evidence that increased release of corticotropin-releasing factor (CRF) in the central nucleus of the amygdala (CeA) contributes to stress responsivity during cocaine withdrawal (WD). Recent studies suggest that tissue plasminogen activator (tPA) in the CeA is a downstream effector protein for CRF after acute “binge” cocaine administration. The purpose of this study was to determine if tPA modulates cocaine WD-induced stress responsivity. Wild-type (WT) and tPA-deficient (tPA −/−) mice were subjected to chronic (14 days) “binge” cocaine (45 mg/kg per day) or its acute (1 day) WD. Extracellular tPA activity, CRF mRNA levels, and plasma corticosterone (CORT) levels were measured in tPA −/− and WT mice. Extracellular tPA activity was reduced by 50% in the CeA and medial amygdala of WT mice after chronic cocaine and returned to basal levels after acute WD. Unlike WT mice, tPA −/− mice did not display elevated amygdalar CRF mRNA levels during cocaine WD. In comparison to WT mice, tPA −/− mice showed a blunted plasma CORT response during acute WD. These results demonstrate that tPA activity in the amygdala (Amy) is altered by chronic cocaine exposure, and further suggest an involvement of tPA in modulating amygdalar CRF stress responsive system and hypothalamic–pituitary–adrenal axis in response to acute cocaine WD.
tPA; cocaine withdrawal; CRF; amygdala; HPA axis
Synovial sarcomas commonly occur in the soft tissue of the extremities, while a primary occurrence in the mediastinum is quite rare. The current study reports the case of an 11-year-old male who presented with a neck mass, which computed tomography showed was due to a giant mediastinal mass involving the thyroid gland. The tumor was resected by thoracotomy and diagnosed as monophasic synovial sarcoma by histopathology. The patient received adjuvant combination chemotherapy and radiation therapy following surgery. At the 3-month follow-up, no local tumor recurrence was found. The present case report highlights the significance of recognizing the unusual presentation and clinical manifestation of synovial sarcoma to aid clinical management. Written informed consent was obtained from the patient’s family.
synovial sarcoma; mediastinum; neck mass
In a previous study, steady-state methadone treatment was found to prevent associative cocaine learning, as well as related decreases in mRNA expression of preprohypocretin/preproorexin (ppHcrt) in the lateral hypothalamus (LH) and dopamine D2 receptor (DR2) in the caudate-putamen (CP), and increases in mu-opioid receptor in the ventral striatum of rats. To investigate whether the same regimen of methadone exposure could prevent the incubation of cocaine sensitization and related alterations in gene expression, male Sprague–Dawley rats received 45 mg/kg/day steadydose “binge” cocaine administration (IP) for 14 days followed by mini-pumps releasing 30 mg/kg/day methadone (SC). After 14 days of methadone, and a subsequent 10-day drug-free period, all rats were tested for sensitization (cocaine test dose: 15 mg/kg) and brain tissue was collected to quantify mRNA expression. Rats exposed to cocaine displayed cocaine-induced stereotypy at test, as well as enhanced ppHcrt mRNA in the LH and reduced DR2 mRNA in the CP. Importantly, these alterations were significantly reduced in rats treated with methadone following cocaine. These results suggest that steady-state methadone can interfere with the incubation of neuroadaptations underlying changes in behavioral responses to cocaine and cocaine-associated stimuli, and that these effects can be observed even after withdrawal from methadone.
Cocaine; Methadone; Sensitization; Stereotypy; Gene expression; Preprohypocretin/preproorexin; Dopamine D2 receptor; Lateral hypothalamus; Striatum
Evidence implicates cyclin D1 (CCND1) G870A polymorphisms as risk factors for various cancers. An increasing number of investigations have been conducted on the association of CCND1 G870A polymorphisms with susceptibility to oral carcinoma, and have yielded inconclusive results. The aim of the present study was to derive a more precise estimation of the correlation. Meta-analyses examining the association between CCND1 G870A polymorphisms and oral carcinoma were performed. Separate analyses on ethnicity, smoking status and control sources were also implemented. Eligible studies were identified prior to February 2012. From the overall data from 1,128 cases and 1,276 controls, no associations of CCND1 G870A polymorphisms with oral carcinoma were observed [AA vs. GG: odds ratio (OR)=1.06; 95% confidence interval (CI), 0.62–1.82; dominant model: OR=1.04; 95% CI, 0.76–1.43; recessive model: OR=1.06; 95% CI, 0.70–1.59]. In the subgroup analysis by ethnicity, smoking status and control sources, no significant associations of CCND1 G870A polymorphisms and oral cancer were observed for the three genetic models. Collectively, the data failed to suggest CCND1 G870A polymorphism as a low-penetrant risk factor for developing oral carcinoma. Additional studies with large sample sizes concerning different ethnicities in different areas are required.
cyclin D1 G870A; mouth neoplasm; susceptibility; meta-analysis; polymorphism
Plant RNA-dependent RNA Polymerase 1 (RDR1) is an important element of the RNA silencing pathway in the plant defense against viruses. RDR1 expression can be elicited by viral infection and salicylic acid (SA), but the mechanisms of signaling during this process remains undefined. The involvement of hydrogen peroxide (H2O2) and nitric oxide (NO) in RDR1 induction in the compatible interactions between Tobacco mosaic tobamovirus (TMV) and Nicotiana tabacum, Nicotiana benthamiana, and Arabidopsis thaliana was examined. TMV inoculation onto the lower leaves of N. tabacum induced the rapid accumulation of H2O2 and NO followed by the increased accumulation of RDR1 transcripts in the non-inoculated upper leaves. Pretreatment with exogenous H2O2 and NO on upper leaf led to increased RDR1 expression and systemic TMV resistance. Conversely, dimethylthiourea (an H2O2 scavenger) and 2-(4-carboxyphenyl)- 4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (an NO scavenger) partly blocked TMV- and SA-induced RDR1 expression and increased TMV susceptibility, whereas pretreatment with exogenous H2O2 and NO failed to diminish TMV infection in N. benthamiana plants with naturally occurring RDR1 loss-of-function. Furthermore, in N. tabacum and A. thaliana, TMV-induced H2O2 accumulation was NO-dependent, whereas NO generation was not affected by H2O2. These results suggest that, in response to TMV infection, H2O2 acts downstream of NO to mediate induction of RDR1, which plays a critical role in strengthening RNA silencing to restrict systemic viral infection.
To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million nonredundant microbial genes, derived from 576.7 Gb sequence, from faecal samples of 124 European individuals. The gene set, ~150 times larger than the human gene complement, contains an overwhelming majority of the prevalent microbial genes of the cohort and likely includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, suggesting that the entire cohort harbours between 1000 and 1150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions encoded by the gene set.
Antagonism of the kappa opioid receptor (KOR) has been reported to have anti-depressant-like properties. The dynorphin/KOR system is a crucial neurochemical substrate underlying the pathologies of addictive diseases, affective disorders and other disease states. However, the molecular underpinnings and neuroanatomical localization of the dysregulation of this system have not yet been fully elucidated. Utilizing the Porsolt Forced Swim Test (FST), an acute stressor commonly used as in rodent models measuring antidepressant efficacy, male Sprague-Dawley rats were subject to forced swimming for 15 minutes, treated 1 hour with vehicle or nor-BNI (5 or 10 mg/kg), and then 1 day later subject to FST for five minutes. In accordance with previous findings, nor-BNI dose dependently increased climbing time and reduced immobility. In comparison to control animals not exposed to FST, we observed a significant elevation in prodynorphin (pDyn) mRNA levels following FST using real-time optical PCR in the caudate putamen but not in the nucleus accumbens, hypothalamus, amygdala, frontal cortex, or hippocampus. Nor-BNI treatment did not affect pDyn mRNA levels in comparison to animals that received vehicle. The corresponding brain regions from the opposite hemisphere were analyzed for underlying chromatin modifications of the prodynorphin gene promoter region using chromatin immunoprecipitation with antibodies against specifically methylated histones H3K27Me2, H3K27Me3, H3K4Me2, and H3K4Me3, as well as CREB-1 and MeCP2. Significant alterations in proteins bound to DNA in the Cre-3, Cre-4, and Sp1 regions of the prodynorphin promoter were found in the caudate putamen of the FST saline-treated animals compared to control animals, with no changes observed in the hippocampus. Epigenetic changes resulting in elevated dynorphin levels specifically in the caudate putamen may in part underlie the enduring effects of stress.
Stress; Dynorphin; Histones; CREB; MeCP2; Caudate-Putamen
Schistosoma japonicum is a parasitic flatworm that causes human schistosomiasis, a significant cause of morbidity in China and the Philippines. Here we present a draft genomic sequence for the worm, which is the first reported for any flatworm, indeed for the superphylum Lophotrochozoa. The genome provides a global insight into the molecular architecture and host interaction of this complex metazoan pathogen, revealing that it can exploit host nutrients, neuroendocrine hormones and signaling pathways for growth, development and maturation. Having a complex nervous system and a well developed sensory system, S. japonicum can accept stimulation of the corresponding ligands as a physiological response to different environments, such as fresh water or the tissues of its intermediate and mammalian hosts. Numerous proteinases, including cercarial elastase, are implicated in mammalian skin penetration and haemoglobin degradation. The genomic information will serve as a valuable platform to facilitate development of new interventions for schistosomiasis control.
Although recent studies have clearly demonstrated functional and structural abnormalities in adolescents with internet gaming addiction (IGA), less is known about how IGA affects perfusion in the human brain. We used pseudocontinuous arterial spin-labeling (ASL) perfusion functional magnetic resonance imaging (fMRI) to measure the effects of IGA on resting brain functions by comparing resting cerebral blood flow in adolescents with IGA and normal subjects.
Fifteen adolescents with IGA and 18 matched normal adolescents underwent structural and perfusion fMRI in the resting state. Direct subtraction, voxel-wise general linear modeling was performed to compare resting cerebral blood flow (CBF) between the 2 groups. Correlations were calculated between the mean CBF value in all clusters that survived AlphaSim correction and the Chen Internet Addiction Scale (CIAS) scores, Barratt Impulsiveness Scale-11 (BIS-11) scores, or hours of Internet use per week (hours) in the 15 subjects with IGA.
Compared with control subjects, adolescents with IGA showed significantly higher global CBF in the left inferior temporal lobe/fusiform gyrus, left parahippocampal gyrus/amygdala, right medial frontal lobe/anterior cingulate cortex, left insula, right insula, right middle temporal gyrus, right precentral gyrus, left supplementary motor area, left cingulate gyrus, and right inferior parietal lobe. Lower CBF was found in the left middle temporal gyrus, left middle occipital gyrus, and right cingulate gyrus. There were no significant correlations between mean CBF values in all clusters that survived AlphaSim correction and CIAS or BIS-11 scores or hours of Internet use per week.
In this study, we used ASL perfusion fMRI and noninvasively quantified resting CBF to demonstrate that IGA alters the CBF distribution in the adolescent brain. The results support the hypothesis that IGA is a behavioral addiction that may share similar neurobiological abnormalities with other addictive disorders.
Internet addiction; Internet gaming addiction; Arterial spin-labeling perfusion; fMRI; Cerebral blood flow
Cardiac hypertrophy is a response of the myocardium to increased workload and is characterised by an increase of myocardial mass and an accumulation of extracellular matrix (ECM). As an ECM protein, an integrin ligand, and an angiogenesis inhibitor, all of which are key players in cardiac hypertrophy, mindin is an attractive target for therapeutic intervention to treat or prevent cardiac hypertrophy and heart failure. In this study, we investigated the role of mindin in cardiac hypertrophy using littermate Mindin knockout (Mindin−/−) and wild-type (WT) mice. Cardiac hypertrophy was induced by aortic banding (AB) or angiotensin II (Ang II) infusion in Mindin−/− and WT mice. The extent of cardiac hypertrophy was quantitated by echocardiography and by pathological and molecular analyses of heart samples. Mindin−/− mice were more susceptible to cardiac hypertrophy and fibrosis in response to AB or Ang II stimulation than wild type. Cardiac function was also markedly exacerbated during both systole and diastole in Mindin−/− mice in response to hypertrophic stimuli. Western blot assays further showed that the activation of AKT/glycogen synthase kinase 3β (GSK3β) signalling in response to hypertrophic stimuli was significantly increased in Mindin−/− mice. Moreover, blocking AKT/GSK3β signalling with a pharmacological AKT inhibitor reversed cardiac abnormalities in Mindin−/− mice. Our data show that mindin, as an intrinsic cardioprotective factor, prevents maladaptive remodelling and the transition to heart failure by blocking AKT/GSK3β signalling.
Mindin; Hypertrophy; Remodelling; Signal transduction; AKT
Vaccination is considered as the most effective preventive method to control influenza. The hallmark of influenza virus is the remarkable variability of its major surface glycoproteins, HA and NA, which allows the virus to evade existing anti-influenza immunity in the target population. So it is necessary to develop a novel vaccine to control animal influenza virus. Also we know that the ectodomain of influenza matrix protein 2 (M2e) is highly conserved in animal influenza A viruses, so a vaccine based on the M2e could avoid several drawbacks of the traditional vaccines. In this study we designed a novel tetra-branched multiple antigenic peptide (MAP) based vaccine, which was constructed by fusing four copies of M2e to one copy of foreign T helper (Th) cell epitope, and then investigated its immune responses.
Our results show that the M2e-MAP induced strong M2e-specific IgG antibody,which responses following 2 doses immunization in the presence of Freunds’ adjuvant. M2e-MAP vaccination limited viral replication substantially. Also it could attenuate histopathological damage in the lungs of challenged mice and counteracted weight loss. M2e-MAP-based vaccine protected immunized mice against the lethal challenge with PR8 virus.
Based on these findings, M2e-MAP-based vaccine seemed to provide useful information for the research of M2e-based influenza vaccine. Also it show huge potential to study vaccines for other similarly viruses.
Influenza A virus; Influenza; M2e; Synthetic peptide vaccine
We propose an augmented classical least squares (ACLS) calibration method for quantitative Raman spectral analysis against component information loss. The Raman spectral signals with low analyte concentration correlations were selected and used as the substitutes for unknown quantitative component information during the CLS calibration procedure. The number of selected signals was determined by using the leave-one-out root-mean-square error of cross-validation (RMSECV) curve. An ACLS model was built based on the augmented concentration matrix and the reference spectral signal matrix. The proposed method was compared with partial least squares (PLS) and principal component regression (PCR) using one example: a data set recorded from an experiment of analyte concentration determination using Raman spectroscopy. A 2-fold cross-validation with Venetian blinds strategy was exploited to evaluate the predictive power of the proposed method. The one-way variance analysis (ANOVA) was used to access the predictive power difference between the proposed method and existing methods. Results indicated that the proposed method is effective at increasing the robust predictive power of traditional CLS model against component information loss and its predictive power is comparable to that of PLS or PCR.
Steady-state fluorence imaging and time-resolved fluorescence imaging are two important areas in fluorescence imaging research. Fluorescence lifetime imaging is an absolute measurement method which is independent of excitation laser intensity, fluorophore concentration, and photobleaching compared to fluorescence intensity imaging techniques. Time-gated fluorescence lifetime imaging microscopy (FLIM) can provide high resolution and high imaging frame during mature FLIM methods. An abstract time-gated FLIM model was given, and important temporal parameters are shown as well. Aiming at different applications of steady and transient fluorescence processes, two different operation modes, timing and lifetime computing algorithm are designed. High resolution and high frame can be achieved by one-excitation one-sampling mode and least square algorithm for steady imaging applications. Correspondingly, one-excitation two-sampling mode and rapid lifetime determination algorithm contribute to transient fluorescence situations.
Previous genome-wide association studies (GWASs) identified multiple susceptibility loci that have highlighted the important role of TLR (Toll-like receptor) and CARD (caspase recruitment domain) genes in leprosy. A large three-stage candidate gene-based association study of 30 TLR and 47 CARD genes was performed in the leprosy samples of Chinese Han. Of 4363 SNPs investigated, eight SNPs showed suggestive association (P < 0.01) in our previously published GWAS datasets (Stage 1). Of the eight SNPs, rs2735591 and rs4889841 showed significant association (P < 0.001) in an independent series of 1504 cases and 1502 controls (Stage 2), but only rs2735591 (next to BCL10) showed significant association in the second independent series of 938 cases and 5827 controls (Stage 3). Rs2735591 showed consistent association across the three stages (P > 0.05 for heterogeneity test), significant association in the combined validation samples (Pcorrected = 5.54 × 10−4 after correction for 4363 SNPs tested) and genome-wide significance in the whole GWAS and validation samples (P = 1.03 × 10−9, OR = 1.24). In addition, we demonstrated the lower expression of BCL10 in leprosy lesions than normal skins and a significant gene connection between BCL10 and the eight previously identified leprosy loci that are associated with NFκB, a major regulator of downstream inflammatory responses, which provides further biological evidence for the association. We have discovered a novel susceptibility locus on 1p22, which implicates BCL10 as a new susceptibility gene for leprosy. Our finding highlights the important role of both innate and adaptive immune responses in leprosy.
Substituted toluenyl groups are considered as close isosteres of the thymine residue. They can be recognized by DNA polymerases as if they were thymine. These toluene derivatives are generally inert toward radical additions, including the [2+2] photo-cycloadditions, due to the stable structure of the aromatic ring and are usually used as solvents for radical reactions. Surprisingly, after incorporating toluene into the dinucleotide framework, we found that the UV excited thymine residue readily dimerizes with the toluenyl moiety through a [2+2] photo-addition reaction. Furthermore, the reaction site on the toluenyl moiety is not the C5=C6 bond, as commonly observed in cyclobutane pyrimidine dimers, but the C4=C5 or C3=C4 instead. Such a reaction pattern suggests that in the stacked structure, it is one of these bonds, not the C5=C6, that is close to the thymine C5=C6 bond. A similar structural feature is found in DNA duplex with a thymine replaced by a 2,4-difluorotoluene. Our results argue that although the substituted toluenyl moieties closely mimic the size and shape of the thymine residue, their more hydrophobic nature determines that they stack on DNA bases differently from the natural thymine residue and likely cause local conformational changes in duplex DNA.
cyclobutane pyrimidine dimers; DNA; photochemistry; stereochemistry; thymine
The study of habitat selection and diet has a long history in ecology. This is often used to assess the functional roles of wetland in biodiversity conservation. Shifting habitat and diet may be one of the survival strategies during extremely adverse conditions. Therefore, sudden changes in habitat selection may indicate the deterioration of the habitat quality, and management interventions are necessary. Siberian crane (Grus leucogeranus) became critically endangered due to loss of habitat, and is currently a global conservation focus. Every winter, more than 95% of the species' global population congregates at Poyang Lake, and feeds on tubers of Vallisneria spiralis in shallow water and mudflat habitat. In this study, we reported the first sighting of large numbers of Siberian cranes foraging at wet meadows, where they fed on a different plant, Potentilla limprichtii due to extreme scarcity of their preferred tuber. To understand how well the cranes adapted to such unusual habitat, field surveys to assess the distribution of cranes across different habitats, and food availability in each habitat were carried out in the winter of 2011. Field observations on crane behaviors at different habitats were also conducted. Results show that cranes displayed significantly different behavior patterns when using the wet meadow, compared to the crane's optimal habitat - shallow water and mudflat. Both juveniles and adults spent significantly less time foraging, and more time alerting in meadows than in shallow waters and mudflats. These results indicated that the meadow might be a suboptimal wintering ground for Siberian crane, which helped the cranes survive from extreme unfavorable conditions. To some degree, this finding alleviates the general concern over the fluctuating of its food resources which was caused by hydrological disturbances. However, more studies are needed to assess the consequences of such diet and habitat shift for crane survival.
In recent years, acute outbreaks of epizootic diarrhea have occurred on many swine farms in China. Although the putative causative virus of the disease was not isolated, the genomic sequence of porcine epidemic diarrhea virus (PEDV) was consistently detected from feces of diseased pigs by reverse transcription-PCR (RT-PCR). Here we report a complete genome sequence of PEDV which is apparently different from those of early PEDV circulated in Chinese swine herds.
hUC-MSCs hold great promise in vitro neuronal differentiation and therapy for neurodegenerative disorders including Parkinson’s disease. Recent studies provided that Lmx1α play an important role in the midbrain dopamine cells differentiation. Neurturin is desired candidate gene for providing a neuroprotective to DA neurons. In this study, we investigated a novel neuronal differentiation strategy in vitro with Lmx1α and NTN. We transferred these two genes to hUC-MSCs by recombinant adenovirus combined with Lmx1α regulatory factor and other inductor to improve the efficiency of inducing. Then those induced cells were implanted into the striatum and substantia nigra of MPTP lesioned hemi-parkinsonian rhesus monkeys. Monkeys were monitored by using behavioral test for six months after implantation. The result showed that cells isolated from the umbilical cord were negative for CD45, CD34 and HLA-DR, but were positive for CD44, CD49d, CD29. After those cells were infected with recombinant adenovirus, RT-PCR result shows that both Lmx1α and NTN genes were transcribed in hUC-MSCs. We also observed that the exogenous were highly expressed in hUC-MSCs from immunofluorescence and western blot. Experiments in vitro have proved that secretion NTN could maintain the survival of rat fetal midbrain dopaminergic neurons. After hUC-MSCs were induced with endogenous and exogenous factors, the mature neurons specific gene TH, Pitx3 was transcripted and the neurons specific protein TH, β-tubulinIII, NSE, Nestin, MAP-2 was expressed in those differentiated cells. In addition, the PD monkeys, transplanted with the induced cells demonstrated the animals’ symptoms amelioration by the behavioral measures. Further more, pathological and immunohistochemistry data showed that there were neuronal-like cells survived in the right brain of those PD monkeys, which may play a role as dopaminergic neurons. The findings from this study may help us to better understand the inside mechanisms of PD pathogenesis and may also help developing effective therapy for Parkinson’s disease.
Transcriptome analysis is a powerful tool to obtain large amount genome-scale gene expression profiles. Despite its extensive usage to diverse biological problems in the last decade, transcriptomic researches approaching the zebrafish embryonic development have been very limited. Several recent studies have made great progress in this direction, yet the large gap still exists, especially regarding to the transcriptome dynamics of embryonic stages from early gastrulation onwards. Here, we present a comprehensive analysis about the transcriptomes of 9 different stages covering 7 major periods (cleavage, blastula, gastrula, segmentation, pharyngula, hatching and early larval stage) in zebrafish development, by recruiting the RNA-sequencing technology. We detected the expression for at least 24,065 genes in at least one of the 9 stages. We identified 16,130 genes that were significantly differentially expressed between stages and were subsequently classified into six clusters. Each revealed gene cluster had distinct expression patterns and characteristic functional pathways, providing a framework for the understanding of the developmental transcriptome dynamics. Over 4000 genes were identified as preferentially expressed in one of the stages, which could be of high relevance to stage-specific developmental and molecular events. Among the 68 transcription factor families active during development, most had enhanced average expression levels and thus might be crucial for embryogenesis, whereas the inactivation of the other families was likely required by the activation of the zygotic genome. We discussed our RNA-seq data together with previous findings about the Wnt signaling pathway and some other genes with known functions, to show how our data could be used to advance our understanding about these developmental functional elements. Our study provides ample information for further study about the molecular and cellular mechanisms underlying vertebrate development.
Upon initial contact with a virus, host cells activate a series of cellular signaling cascades that facilitate viral entry and viral propagation within the cell. Little is known about how the human astrovirus (HAstV) exploits signaling cascades to establish an infection in host cells. Recent studies showed that activation of extracellular signal-regulated kinase 1/2 (ERK1/2) is important for HAstV infection, though the involvement of other signaling cascades remains unclear.
A panel of kinase blockers was used to search for cellular signaling pathways important for HAstV1 infection. To determine their impact on the infectious process, we examined viral gene expression, RNA replication, and viral RNA and capsid protein release from host cells.
Inhibitors of phosphoinositide 3-kinase (PI3K) activation interfered with the infection, independent of their effect on ERK 1/2 activation. Activation of the PI3K signaling cascade occurred at an early phase of the infection, judging from the timeframe of Akt phosphorylation. PI3K inhibition at early times, but not at later times, blocked viral gene expression. However, inhibiting the downstream targets of PI3K activation, Akt and Rac1, did not block infection. Inhibition of protein kinase A (PKA) activation was found to block a later phase of HAstV1 production.
Our results reveal a previously unknown, essential role of PI3K in the life cycle of HAstV1. PI3K participates in the early stage of infection, possibly during the viral entry process. Our results also reveal the role of PKA in viral production.
Astrovirus; Signal transduction; PI3K; ERK1/2
Radiotherapy is an effective treatment for nasopharyngeal carcinoma (NPC). A number of thyroid dysfunctions are induced by damage resulting from the relatively high doses of radiation administered to the thyroid and pituitary gland during radiotherapy. Hypothyroidism constitutes the most frequent type of thyroid dysfunction induced by NPC radiotherapy, while hyperthyroidism, particularly Grave’s disease, is extremely rare. The present study describes the case of a 40-year-old male who presented with Grave’s disease 2 years after receiving radiotherapy for the treatment of NPC. The patient exhibited swelling of the eyes, an increased appetite, decreased levels of thyroid-stimulating hormone, increased levels of triiodothyronine (T3) and thyroxine (T4) demonstrated by the examination of thyroid function and enlargement of the bilateral intraocular rectus revealed by CT scan. The patient’s symptoms were ameliorated following treatment with propylthiouracil and propranolol for 1 month, and the levels of T3 and T4 were restored to normal. The pathophysiological mechanism of radiotherapy-induced hyperthyroidism has yet to be elucidated. Hyperthyroidism is often neglected as several of its clinical manifestations are similar to other complications observed during and following cancer treatment. Therefore, it is necessary to monitor thyroid function following head and neck radiotherapy.
Grave’s disease; radiotherapy; nasopharyngeal carcinoma